DIVERSITY OF CTL EPITOPES AND CHLAMYDIA

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We have found previously that cytotoxic T-lymphocytes (CTL) capable of specific lysis of Chlamydia infected cells are primed during infection with C. trachomatis. Adoptive transfer of cultured CTL into an infected mouse affords protection against C. trachomatis. The experiments in this proposal use a biochemical approach to identify Chlamydia antigens which give rise to the response by CTL. The antigens identified in this proposal will be tested for their ability to engender protective immunity in a vaccine strategy using a recombinant anthrax toxin delivery system. This project will continue to rely on other cores and projects. Initial experiments are also proposed that will address which of these antigensare recognized during human infection. We envision that the vaccine strategy described here would be incorporated into a multivalent vaccine designed to stimulate multiple arms of the immune system. Development of an effective human vaccine would reduce the incidence these infections that are responsible for a great deal of worldwide morbidity. These experiments will not only further our understanding of the importance of CTL in immunity against Chlamydia, but also will provide better understanding of immune recognition by intracellular, vacuolar pathogens in general. Because antigens presented on MHC class I molecules generally are found in the cytoplasm of host cells, identification of a subset of antigens which escape the vacuolar compartment to be processed for presentation on MHC class I molecules to CTL will further our understanding of these very complex host cell-pathogen interactions. The class of antigens identified may also have homologues in other intracellular vacuolar pathogens including Salmonella, Legionella, and Mycobacterium.